Non-sex Hormone-binding Globulin-bound Testosterone Research Articles

Use of statins is associated with lower serum total and non-sex hormone-binding globulin-bound testosterone levels in male participants of the Rotterdam Study

Statins, or HMG-CoA reductase inhibitors, decrease cholesterol production. Because cholesterol is a precursor of the testosterone biosynthesis pathway, there is some concern that statins might lower serum testosterone levels. The objective of the present study was to investigate the association between the use of statins and serum testosterone levels in men. Cross-sectional study within the prospective population-based Rotterdam Study. We included 4166 men with available data on total testosterone, non-sex hormone-binding globulin (SHBG)-bound testosterone, and medication use. Multivariable linear regression analysis was used to compare the differences in serum testosterone levels (nmol/l) between current, past, and never statin users. We considered dose and duration of use. Analyses were adjusted for age, BMI, cardiovascular disease, diabetes mellitus, hypertension, and estradiol levels. We identified 577 current (mean age 64.1 years), 148 past (mean age 64.6 years), and 3441 never (mean age 64.6 years) statin users. Adjusted for all covariables, current statin use of 1-≤ 6 months or >6 months was significantly associated with lower total testosterone levels as compared to non-users (β -1.24, 95% CI -2.17, -0.31, and β -1.14, 95% CI -2.07, -0.20 respectively). Current use of 1-≤ 6 months was also associated with significantly lower non-SHBG-bound testosterone levels (β -0.42, 95% CI -0.82, -0.02). There was a trend toward lower testosterone levels at higher statin doses both for total (P(trend) 2.9 × 10(-5)) and non-SHBG-bound (P(trend) 2.0 × 10(-4)) testosterone. No association between past statin use and testosterone levels was found. We showed that current use of statins was associated with significantly lower serum total and non-SHBG-bound testosterone levels. The clinical relevance of this association should be further investigated.

Gonadal Hormones in Men with Rheumatoid Arthritis — From Onset Through 2 Years

To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs. Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations. The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (r(s) = -0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity. In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome.

Our preliminary family studies have suggested that some female first-degree relatives of women with polycystic ovary syndrome (PCOS) have hyperandrogenemia per se. It was our hypothesis that this may be a genetic trait and thus could represent a phenotype suitable for linkage analysis. To investigate this hypothesis, we examined 115 sisters of 80 probands with PCOS from unrelated families. PCOS was diagnosed by the combination of elevated serum androgen levels and </=6 menses per year with the exclusion of secondary causes. The sisters were compared with 70 healthy age- and weight-comparable control women with regular menses, no clinical evidence of hyperandrogenemia, and normal glucose tolerance. Twenty-two percent of the sisters fulfilled diagnostic criteria for PCOS. In addition, 24% of the sisters had hyperandrogenemia and regular menstrual cycles. Circulating testosterone (T) and nonsex hormone-binding globulin-bound testosterone (uT) levels in both of these groups of sisters were significantly increased compared with unaffected sisters and control women (P < 0.0001 for both T and uT). Probands, sisters with PCOS, and hyperandrogenemic sisters had elevated serum luteinizing hormone levels compared with control women. We conclude that there is familial aggregation of hyperandrogenemia (with or without oligomenorrhea) in PCOS kindreds. In affected sisters, only one-half have oligomenorrhea and hyperandrogenemia characteristic of PCOS, whereas the remaining one-half have hyperandrogenemia per se. This familial aggregation of hyperandrogenemia in PCOS kindreds suggests that it is a genetic trait. We propose that hyperandrogenemia be used to assign affected status in linkage studies designed to identify PCOS genes.

The Insulin-Sensitizing Agent Troglitazone Improves Metabolic and Reproductive Abnormalities in the Polycystic Ovary Syndrome

We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydro-epiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.

Hormonal responses to training and its tapering off in competitive swimmers: relationships with performance.

During a winter training season, the effects of 12 weeks of intense training and 4 weeks of tapering off (taper) on plasma hormone concentrations and competition performance were investigated in a group of highly trained swimmers (n = 8). Blood samples were collected and the swimmers performed their speciality in competition at weeks 10 (mid-season), 22 (pre-taper) and 26 (post-taper). No statistically significant changes were observed in the concentrations of total testosterone (TT), non-sex hormone binding globulin-bound-testosterone (NSBT), cortisol (C), luteinising hormone, thyroid stimulating hormone, triiodothyronine, thyroxine plasma catecholamines, creatine kinase and ammonia during training and taper. Mid-season NSBT: C ratio and the amount of training were statistically related (r = 0.82, P < 0.05). Competition performance slightly declined during intense training [0.52 (SD 2.51)%, NS] and improved during taper [2.32 (SD 1.69)%, P < 0.01]. Changes in performance during training and taper correlated with changes in ratios TT: C (r = 0.86, P < 0.01 and r = 0.81, P < 0.05, respectively) and NSBT: C (r = 0.77, P < 0.05 and r = 0.76, P < 0.05, respectively). In summary, these results showed that the monitored plasma hormones and metabolic indices were unaltered by 12 weeks of intense training and 4 weeks of taper. The TT: C and NSBT: C ratios, however, appeared to be effective markers of the swimmers' performance capacities throughout the training season.

Differential effects of exercise on sex hormone-binding globulin and non-sex hormone-binding globulin-bound testosterone.

The response of total testosterone (T), free testosterone (fT), sex hormone-binding globulin (SHBG) and non-SHBG-bound testosterone (NST) to the same exercise protocol was evaluated in two different experiments on long distance runners. The first experiment was performed in the morning at 0900 hours with nine athletes, while the second was carried out in the afternoon at 1500 hours with seven athletes. During each experiment, each athlete ran for 1 h at the previously determined speed corresponding to 2 mmol.l-1 blood lactate concentration. Three venous blood samples were collected in each experiment: before exercise, at the end of running and after 1 h of recovery. Total T and SHBG showed similar responses: in the first experiment they had decreased after exercise, while in the second they had increased at the end of running. A positive correlation between total T and SHBG concentrations was found at the end of exercise. In both experiments, NST and fT had increased after exercise and decreased to initial concentrations during recovery. The results would suggest the existence of a compensatory mechanism which maintains adequate concentrations of biologically active T when total T concentrations decrease.

Time-dependent changes in serum 3 alpha-androstanediol glucuronide correlate with hirsutism scores after ovarian suppression.

The clinical utility of serum 3 alpha-androstanediol glucuronide level has been controversial. Among the concerns regarding its lack of utility has been the finding that suppression of serum 3 alpha-androstanediol glucuronide does not occur readily with treatment. We hypothesized that because the treatment of hirsutism requires a prolonged duration, a longer observation period is required for changes in serum 3 alpha-androstanediol glucuronide to be measured. Therefore, we studied the clinical and hormonal changes in 11 women treated for hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A progressive reduction in Ferriman-Gallwey scores occurred, which was significant at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide and another peripheral marker, androsterone glucuronide, also fell commensurately. While there was no correlation at 3 months, by 6 weeks a significant correlation had occurred between the suppression in Ferriman-Gallwey scores and the suppression of serum 3 alpha-androstanediol glucuronide and androsterone glucuronide. The suppression of these steroids also correlated with the suppression of non-sex hormone-binding globulin-bound testosterone. These data confirm that markers of peripheral androgen action, particularly serum 3 alpha-androstanediol glucuronide, reflect the clinical manifestation of hirsutism. However, it appears that modifications in peripheral androgen activity (presumably through 5 alpha-reductase activity) are time-dependent, and that serum markers reflect changes after 6 months of treatment.

Sex hormones in postmenopausal women with primary biliary cirrhosis

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p <0.05) elevated serum concentrations of estrone and androstenedione and significantly (p <0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5α-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p> 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p < 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p < 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction. (HEPATOLOGY 1991;13:865–869.)

Sex hormones in postmenopausal women with primary biliary cirrhosis

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Relative diagnostic value of serum non-SHBG-bound testosterone, free androgen index and free testosterone in the assessment of mild to moderate hirsutism.

Recent evidence suggests that steroid hormone loosely bound to albumin is available for target-cell entry. Preliminary studies have suggested that a measure of this fraction, non-sex-hormone-binding globulin-bound testosterone (NSB-T), provides the best in vitro diagnostic test for idiopathic hirsutism. We compared the diagnostic value of NSB-T, total testosterone (T), free testosterone (fT), and the free androgen index (FAI) in supporting the clinical diagnosis in 22 pre-menopausal women with hirsutism. NSB-T supported the diagnosis in 50% of cases, compared with 23% for T, 55% for fT by analogue RIA, and 68% for FAI. We conclude that in mild to moderate hirsutism the measurement of NSB-T does not yield diagnostic information addition to that provided by the FAI.

Lack of correlation of serum estradiol with growth velocity during male pubertal growth.

The adolescent growth spurt in boys is under hormonal control. It is accepted that androgens and growth hormone contribute to male pubertal growth, but the role of estrogens is uncertain even though low-dose estradiol administration stimulates growth in prepubertal boys. In the present work, the correlation of serum testosterone and serum estradiol with growth velocity was studied in 16 pubertal normal boys. The study included correlations of growth velocity with serum nonsex hormone-binding globulin-bound testosterone and with serum nonsex hormone-binding globulin-bound estradiol, which are parameters of serum bioavailable sex hormones. A statistically significant positive correlation was found between serum testosterone and growth velocity but not between serum estradiol and growth velocity. These findings are against the hypothesis that estrogens play a growth promoting role during male puberty.

No Effect of Oral Testosterone Treatment on Sexual Dysfunction in Alcoholic Cirrhotic Men

The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction. Sexual dysfunction was significantly (p less than 0.05) associated with lower serum concentrations of testosterone, non-protein-bound testosterone, and non-sex hormone-binding globulin-bound testosterone. The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared, however, when age, ethanol consumption, and severity of liver disease were included as covariates in the analysis. During follow-up (median 30 mo, range 1-48 mo) sexual dysfunction improved significantly (p less than 0.05) at 6, 12, and 24 mo. Furthermore, the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period (p less than 0.01). However, the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function. In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients.

The Impact of Obesity and Chronic Hyperinsulinemia on Gonadotropin Release and Gonadal Steroid Secretion in the Polycystic Ovary Syndrome

We investigated whether obesity was a marker for a neuroendocrinologically distinct form of the polycystic ovary syndrome (PCO). Further, since women with PCO have significantly higher basal and/or glucose-stimulated plasma insulin levels, we also examined the effects of chronic hyperinsulinemia on gonadotropin and gonadal steroid secretion. Ten obese women (nine with acanthosis nigricans) and five nonobese women (one with acanthosis nigricans) with PCO as well as seven obese and six nonobese women of comparable age and weight in the midfollicular phase of their cycles were studied. Pulsatile gonadotropin release was determined for 6-24 h as well as gonadotroph sensitivity to GnRH (10 micrograms, iv). The obese PCO women had significantly increased basal and glucose-stimulated plasma insulin levels compared to the other groups, the nonobese PCO and the obese normal women had similar insulin levels, and the nonobese normal women had the lowest insulin levels. All four groups had similar plasma estradiol levels. Both the obese and the nonobese PCO women had similar and significantly higher mean plasma LH levels, LH pulse amplitude, and integrated LH responses to GnRH compared to values in both normal groups (P less than 0.01 to P less than 0.001); the obese PCO women did not differ from the nonobese PCO women. The mean LH pulse frequencies per 6 h were similar in the four groups. FSH secretion did not differ significantly in the four groups. The levels of the putative gonadal feedback steroids, plasma total and non-sex hormone-binding globulin-bound testosterone, non-sex hormone-binding globulin-bound estradiol, and estrone, were similar in both PCO groups and were significantly higher than those in both normal groups (all P less than 0.001). The only independent effect of obesity was on plasma androstenedione levels and the androstenedione to estrone ratio, both of which were significantly higher in PCO women than normal women (P less than 0.01 to P less than 0.001), but significantly lower in the obese (PCO and normal) women than in nonobese (PCO and normal) women (P less than 0.05). These findings suggest that 1) the impact, if any, of obesity in PCO is not reflected in discernible changes in gonadotropin release or in the gonadal steroid feedback environment; and 2) insulin does not have a major role in the perpetuation of PCO, since obese and nonobese PCO women had similar reproductive hormone levels despite significantly different degrees of hyperinsulinemia.

The impact of obesity and chronic hyperinsulinemia on gonadotropin release and gonadal steroid secretion in the polycystic ovary syndrome.

We investigated whether obesity was a marker for a neuroendocrinologically distinct form of the polycystic ovary syndrome (PCO). Further, since women with PCO have significantly higher basal and/or glucose-stimulated plasma insulin levels, we also examined the effects of chronic hyperinsulinemia on gonadotropin and gonadal steroid secretion. Ten obese women (nine with acanthosis nigricans) and five nonobese women (one with acanthosis nigricans) with PCO as well as seven obese and six nonobese women of comparable age and weight in the midfollicular phase of their cycles were studied. Pulsatile gonadotropin release was determined for 6-24 h as well as gonadotroph sensitivity to GnRH (10 micrograms, iv). The obese PCO women had significantly increased basal and glucose-stimulated plasma insulin levels compared to the other groups, the nonobese PCO and the obese normal women had similar insulin levels, and the nonobese normal women had the lowest insulin levels. All four groups had similar plasma estradiol levels. Both the obese and the nonobese PCO women had similar and significantly higher mean plasma LH levels, LH pulse amplitude, and integrated LH responses to GnRH compared to values in both normal groups (P less than 0.01 to P less than 0.001); the obese PCO women did not differ from the nonobese PCO women. The mean LH pulse frequencies per 6 h were similar in the four groups. FSH secretion did not differ significantly in the four groups. The levels of the putative gonadal feedback steroids, plasma total and non-sex hormone-binding globulin-bound testosterone, non-sex hormone-binding globulin-bound estradiol, and estrone, were similar in both PCO groups and were significantly higher than those in both normal groups (all P less than 0.001). The only independent effect of obesity was on plasma androstenedione levels and the androstenedione to estrone ratio, both of which were significantly higher in PCO women than normal women (P less than 0.01 to P less than 0.001), but significantly lower in the obese (PCO and normal) women than in nonobese (PCO and normal) women (P less than 0.05). These findings suggest that 1) the impact, if any, of obesity in PCO is not reflected in discernible changes in gonadotropin release or in the gonadal steroid feedback environment; and 2) insulin does not have a major role in the perpetuation of PCO, since obese and nonobese PCO women had similar reproductive hormone levels despite significantly different degrees of hyperinsulinemia.

Androgen therapy of hypogonadal men with transscrotal testosterone systems

The need for improved controlled delivery of testosterone to hypogonadal men stimulated the development of a self-adherent transscrotal testosterone system to provide programmed testosterone delivery through the uniquely permeable scrotal skin. In this short- and long-term efficacy trial, the responses of testosterone and its metabolites to the application of transscrotal testosterone systems of varying testosterone content were compared with the response to 200 mg of testosterone enanthate. Daily transscrotal testosterone system administration resulted in a rapid increase of testosterone and bioavailable, nonsex hormone binding globulin-bound testosterone levels to normal, peaking at two hours, followed by a slow decline over 23 hours, resembling the diurnal variation of endogenous testosterone. One year of daily transscrotal testosterone system therapy demonstrated continued reliable absorption of testosterone and suppression to normal of the luteinizing hormone in two of three patients. There was a greatly disproportionate increase of serum dihydrotestosterone over testosterone, suggesting 5-alpha reduction at the scrotal site. The subjects reported marked subjective improvement. Thus, the transscrotal testosterone system is a novel, effective, and well-tolerated method of delivering testosterone to hypogonadal patients.

Changes in serum sex hormone-binding globulin and in serum non-sex hormone-binding globulin-bound testosterone during prepuberty in boys

Much evidence suggests that sex hormone-binding globulin (SHBG) influences the delivery of sex steroids to cells, probably by playing an important role in the distribution of serum sex hormones between SHBG-bound, albumin (HSA)-bound and free fractions. Recent evidence also suggests that HSA-bound testosterone (T), the major constituent of non-sex hormone-binding globulin-bound T, is biologically important. To examine the potential exposure of peripheral tissues to T during prepubertal years, the serum concentration of SHBG as well as the distribution of serum T in SHBG-bound, HSA-bound, free and non-SHBG-bound fractions was studied in 80 normal boys aged 0.5–14 yr, all at Tanner's stage G1 of sexual development. A gradual decrease in serum SHBG as a function of age was found without significant changes in the K a of SHBG-dihydrotestosterone association. While regression analysis of serum total T vs age showed a 2.6-fold increase from 0.5 to 14 yr of age, those of non-SHBG-found, HSA-bound and free T vs age showed 8- to 9-fold increases during the same period. On the other hand, SHBG-bound T had only a 1.9-fold increase. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6 to 30.4%, the relative increment being greater for HSA-bound T than for free T. It is concluded that, with advancing age, there is a progressive increase in the T exposure of all tissues in normal prepubertal boys. It is speculated that, at the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.

Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism.

Recent evidence suggests that the biologically active testosterone includes both the free and albumin-bound fractions, while the sex hormone-binding globulin (SHBG)-bound steroid dissociates less readily. To examine the significance of the non-SHBG-bound testosterone (i.e. free plus albumin bound) in hyperandrogenism, we obtained single blood samples from 17 normal women, 20 regularly menstruating but hirsute women, and 20 oligoamenorrheic hirsute women. Each serum sample was analyzed for total testosterone by RIA, SHBG-binding capacity was determined by protein precipitation with 50% saturated (NH4)2SO4, and albumin was measured by colorimetry. Non-SHBG-bound and free testosterone and the testosterone to SHBG molar ratio were then calculated. Non-SHBG-bound testosterone was also assayed using differential protein precipitation. There were significant differences among the groups in the mean values of all variables (all P less than 0.05) except albumin. Measurement and calculation of serum non-SHBG-bound testosterone produced similar results, suggesting that the binding equation is valid. There was considerable overlap between normal (control mean +/- 2 SD) and abnormal subjects in all variables except non-SHBG-bound testosterone, for which only 3 regularly menstruating and 2 oligoamenorrheic hirsute subjects were in the normal range. As total testosterone levels increased, there was a significant increase in the ratio of non-SHBG-bound testosterone to free testosterone. These data suggest that albumin becomes increasingly more important in testosterone binding as the total serum testosterone level increases and that non-SHBG-bound testosterone may be the optimal marker to identify hyperandrogenism in hirsute women.